2-79086471-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006507.4(REG1B):c.217G>T(p.Val73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
REG1B
NM_006507.4 missense
NM_006507.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 0.400
Genes affected
REG1B (HGNC:9952): (regenerating family member 1 beta) This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV based on the primary structures of the encoded proteins. This gene encodes a protein secreted by the exocrine pancreas that is highly similar to the REG1A protein. The related REG1A protein is associated with islet cell regeneration and diabetogenesis, and may be involved in pancreatic lithogenesis. Reg family members REG1A, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2785778).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
REG1B | NM_006507.4 | c.217G>T | p.Val73Leu | missense_variant | 4/6 | ENST00000305089.8 | NP_006498.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
REG1B | ENST00000305089.8 | c.217G>T | p.Val73Leu | missense_variant | 4/6 | 1 | NM_006507.4 | ENSP00000303206 | P1 | |
REG1B | ENST00000476554.1 | n.629G>T | non_coding_transcript_exon_variant | 3/3 | 1 | |||||
REG1B | ENST00000479258.5 | n.324G>T | non_coding_transcript_exon_variant | 4/4 | 1 | |||||
REG1B | ENST00000454188.5 | c.70G>T | p.Val24Leu | missense_variant | 2/4 | 3 | ENSP00000387410 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727152
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74426
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2021 | The c.217G>T (p.V73L) alteration is located in exon 4 (coding exon 3) of the REG1B gene. This alteration results from a G to T substitution at nucleotide position 217, causing the valine (V) at amino acid position 73 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Uncertain
T;T
Polyphen
0.72
.;P
Vest4
0.29
MutPred
0.78
.;Gain of sheet (P = 0.1539);
MVP
MPC
0.012
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at